LSD (0.93 Mumol/kg i.v.) significantly increased the turnover rate of acetylcholine in the frontal cortex, but not in the striatum or hippocampus of the rat brain. In contrast, an equimolar dose of 2-bromo-LSD, a nonhallucinogenic congener of LSD, did not affect the acetylcholine turnover rate in any of the brain areas examined. Moreover, this effect of LSD on cortical cholinergic dynamics was not mimicked by several putative serotonin agonists. These results argue against a direct postsynaptic serotonin agonist effect of LSD on the soma and/or terminals of cortical cholinergic neurons. The i.vt. administration of 2-chloroadenosine, an adenosine receptor agonist, decreased the turnover rate of acetylcholine in the hippocampus and cortex, but not in the striatum. This effect of 2-chloroadenosine was antoganized by the i.vt. administration of theophylline, an adenosine receptor antagonist, suggesting that an activation of adenosine receptors may be operative in this action of 2-chloroadenosine.